Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Critical care medicine-related treatment is an interdisciplinary and multi-professional process,often leading to secondary or concomitant mental disorders in clinical practice.Currently,there is no consensus on the pharmacological treatment of related mental illnesses in China.The Chinese Society of Psychosomatic Medicine collaborated with the Critical Care Medicine expert group to form a consensus writing expert group.After a systematic review of relevant literature,summarizing published domestic and foreign literature,and extensive discussions,the consensus was developed.The consensus elaborates on the principles and processes of the standardized use of psychotropic drugs in critical care medicine,as well as the clinical indications,precautions,and specific drug selection of various psychiatric medications,providing feasible suggestions and guidance for the clinical application of psychiatric medications in the intensive care unit.

Objective:To explore the neuroprotective effect and molecular mechanism of sulforaphane (SFN) on acute carbon monoxide poisoning (ACOP) in rats.Methods:A total of 135 healthy adult male Sprague-Dawley (SD) rats were randomly divided into normal control group, ACOP model group, and SFN intervention group, with 45 rats in each group. The ACOP animal model was reproduced using carbon monoxide (CO) inhalation in a hyperbaric oxygen chamber, while the normal control group was allowed to breathe fresh air freely. The rats in the SFN intervention group received intraperitoneal injection of SFN at a dose of 20 mg/kg once daily starting 2 hours after CO poisoning and continuing until euthanasia. The normal control group and the ACOP model group received equivalent volume of saline injection. Three rats from each group were sacrificed 1 day after intervention to observe the changes in the ultrastructure of neuronal mitochondria in brain tissues under transmission electron microscopy. Six rats from each group were evaluated for cognitive function using neurobehavioral test 7 days after intervention. Brain tissues of 6 rats in each group were collected 1, 3, and 7 days after intervention, and the expressions of phosphorylated-adenosine monophosphate-activated protein kinase (p-AMPK), mitofusin 2 (MFN2), and dynamin-related protein 1 (DRP1) were detected using immunohistochemistry staining and Western blotting. Linear regression analysis was performed to assess the correlations between the expression levels of above proteins.Results:In the normal control group, the rats did not exhibit any abnormalities in cognitive function or the ultrastructure of neuronal mitochondria in brain tissues. ACOP induced cognitive impairment and ultrastructural injury to neuronal mitochondria in rats. However, SFN significantly improved cognitive function in poisoned rats and mitigated the extent of neuronal mitochondrial damage. Over poisoning time, the expression levels of p-AMPK and MFN2 in the brain tissues of ACOP rats were gradually decreased, while the expression level of DRP1 was gradually increased. Compared with the normal control group, the ACOP model group showed significant differences in the expressions of p-AMPK, MFN2, and DRP1. After SFN intervention, the expression levels of above proteins were significantly reversed. Compared with the ACOP model group, the SFN intervention group exhibited a marked increase in the expressions of p-AMPK and MFN2 [p-AMPK positive expression ( A value): 0.226±0.003 vs. 0.177±0.033, p-AMPK protein (p-AMPK/GAPDH): 1.41±0.05 vs. 0.89±0.05, MFN2 positive expression ( A value): 0.241±0.004 vs. 0.165±0.007, MFN2 protein (MFN2/GAPDH): 1.33±0.04 vs. 0.79±0.03, all P < 0.05], along with a significant decrease in DRP1 expression [DRP1 positive expression ( A value): 0.103±0.002 vs. 0.214±0.011, DRP1 protein (DRP1/GAPDH): 1.00±0.03 vs. 1.50±0.03, both P < 0.05]. Linear regression analysis revealed a strong negative linear correlation between DRP1 protein expression and MFN2, p-AMPK protein expressions ( R2 values were 0.977 and 0.971, both P < 0.01), and a positive linear correlation between p-AMPK protein expression and MFN2 protein expression ( R2 = 0.985, P < 0.01). Conclusion:SFN can help maintain neuronal mitochondrial homeostasis by activating the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, thereby alleviating neuronal injury caused by ACOP.

Objective:To investigate the factors influencing fall risk scores in elderly individuals.Methods:A total of 4 419 individuals were randomly selected using the cluster sampling method from Beijing, Nanning(Guangxi), and Yinchuan(Ningxia).Data on demographic characteristics and fall-related incidents were gathered and analyzed for their correlation with fall risk scores.Results:The fall risk score showed significant associations with various factors, such as the history of falls within one year( β=-3.607, 95% CI: -3.881 to -3.332), care methods( β=2.442, 95% CI: 2.226 to 2.658), exercise( β=0.714, 95% CI: 0.443 to 0.986), retirement( β=-0.585, 95% CI: -0.819 to -0.351), age( β=0.173, 95% CI: 0.159 to 0.187), and use of walking aids( β=-3.737, 95% CI: -4.054 to -3.421). Conclusions:Fall risk scores in older adults are influenced by a variety of factors.Factors such as no history of falls within the past year, living independently, engaging in physical activity, and being employed may contribute to lower fall risk scores in older adults.

Objective To investigate the clinical and imaging features of extralobar pulmonary sequestration(ELS)with torsion.Methods The clinical and imaging data,surgical records and pathological results of four ELS children with torsion were analyzed ret-rospectively.Results All four children presented with abdominal pain,and all CT scans showed soft tissue masses on the medial side of the lower lobe,and there were 2 masses with long fusculine-shaped in the right pleural cavity,2 round masses in the left pleural cavity,all of which were accompanied by pleural effusion and poor ventilation of adjacent lung lobes.There were 1 case without enhance-ment,1 case with mild enhancement,and 2 cases with simple marginal linear enhancement.There were no patients with definitive supplying artery and 3 cases with peripheral post-intercostal dilated veins.Intraoperative ELS combined with torsion was shown,and the nutrient artery were derived from the thoracic aorta.All ELS showed bleeding and necrosis according to the pathological results,and 1 case was complicated with congenital pulmonary airway malformation(type 2).Conclusion ELS combined with torsion is mostly abdominal pain as the first symptom,and there are soft tissue mass adjacent to the lower lobe with pleural effusion on the affected side as the imaging features with no,mild or marginal linear enhancement,with no supplying artery,and with intracostal posterior venous expansion.

OBJECTIVE To investigate whether gas-trodin(GAS)plays a neuroprotective role by activating PI3K/Akt/BACH1 signaling axis to improve glycolytic func-tion.METHODS HT22 cells were treated with Aβ25-35 for 24 h to establish cell damage model.GAS pretreated HT22 cells for 2 h,and Akt agonist SC79,Akt inhibitor MK2206,PI3K inhibitor LY294002 were added 0.5 h before GAS treatment to detect their protective mecha-nisms.Pharmacodynamic research of GAS in this model were divided into six groups:control group,GAS group(GAS 10 μmol·L-1),model group(Aβ25-35 20 μmol·L-1),model +GAS 2.5,5 and 10 μ mol·L-1 group).Mecha-nism research of GAS in this model was divided into 6 groups:control group,Aβ25-35 20 μmol·L-1 group,Aβ25-35 20 μmol·L-1 + GAS 10 μmol·L-1 group,Aβ25-35 + SC79 group(Aβ25-35 20 μmol·L-1 +SC79 10 μmol·L-1),Aβ25-35+MK2206+GAS group(A β 25-35 20 μ mol·L-1 +MK2206 10 μmol·L-1+GAS 10 μmol·L-1),Aβ25-35+LY294002+GAS group(Aβ25-35 20 μmol·L-1+LY294002 10 μmol·L-1+GAS 10 μmol·L-1).Cell viability was detected by MTT,mor-phological changes of cells were observed by micro-scope,ATP content was detected by chemilumines-cence,and pyruvate(PA)content was detected by colo-rimetry.Western blotting was used to detect the protein levels of transcription factor BACH1,key glycolysis enzyme hexokinase(HK1)and PI3K/Akt signaling path-way related proteins PI3K,p-PI3K,Akt and p-Akt.RESULTS The results showed that compared with the control group,the cell morphology of HT22 cells damaged by Aβ25-35 was damaged,the number of cells decreased,the cell body became smaller,the number of dead cells increased,the cell survival rate,ATP and PA contents decreased significantly,and the protein expressions of p-PI3K,p-Akt,BACH1 and HK1 were significantly down-regulated.GAS treatmentcansignificantlyimprovethemor-phology of HT22 cells damaged by Aβ25-35,increase cell survival rate,ATP and PA contents,and up-regulate the expression of p-PI3K,p-Akt,BACH1 and HK1 proteins.SC79 also significantly increased cell survival rate,ATP content,protein expression of BACH1 and HK1.However,the above ameliorative effect of GAS on HT22 cell dam-age induced by Aβ25-35 was antagonized by LY294002 and MK2206.CONCLUSION GAS exerts a neuroprotec-tive effect on Aβ25-35-induced HT22 cell injury by improv-ing glycolytic function through activating PI3K/Akt/BACH1 signaling axis.

Objectives:To investigate the effect of fat suppression (FS) T 2WI on the interobserver agreement and diagnostic performance of clear cell likelihood score version 2.0 (ccLS v2.0) for clear cell renal cell carcinoma (ccRCC). Methods:In this retrospective study, the MR images of 111 patients with pathologically confirmed small renal masses (SRM) from January to December 2021 were analyzed in the First Medical Centre, Chinese PLA General Hospital. Of the 111 SRM, 82 cases were ccRCC and 29 cases were non-ccRCC. Two radiologists independently assessed ccLS scores based on T 2WI signal intensity (hypointense, isointense, hyperintense) and other MRI features (ccLS-T 2WI). After a one-month interval, the ccLS scores were independently evaluated utilizing the frequency-selective saturation FS-T 2WI and other MRI features (ccLS-FS-T 2WI). Fisher′s exact test was used to compare the difference in SRM signal intensity on T 2WI and FS-T 2WI. The weighted Kappa test was performed to assess the interobserver agreement of the two radiologists, and differences in the weighted Kappa coefficients were compared using the Gwet consistency coefficient. Receiver operating characteristic curves were drawn to evaluate the diagnostic performance of ccLS-T 2WI and ccLS-FS-T 2WI in diagnosing ccRCC, and the area under the curve (AUC) was compared utilizing the DeLong test. Results:The signal intensity of 111 SRM on T 2WI and FS-T 2WI had statistically significant difference (χ 2=126.33, P<0.001), consistent in 88 cases (79.3%) and varied in 23 cases (20.7%). The weighted Kappa coefficient of ccLS-T 2WI was 0.57 (95%CI 0.45-0.69) between the two radiologists, and the weighted Kappa coefficient of ccLS-FS-T 2WI was 0.55 (95%CI 0.42-0.67), and the difference was not statistically significant ( t=-0.65, P=0.520). The AUC of ccLS-T 2WI for ccRCC diagnosis was 0.92 (95%CI 0.86-0.97), while the AUC of ccLS-FS-T 2WI for ccRCC diagnosis was 0.91 (95%CI 0.85-0.96), and the difference was not statistically significant ( Z=1.50, P=0.133). Conclusions:The interobserver agreement and diagnostic performance of ccLS v2.0 based on T 2WI and FS-T 2WI sequences for ccRCC are comparable, and FS-T 2WI is applicable for the clinical application of ccLS v2.0.

Objective:To investigate the clinical and MRI features of the mixed epithelial and stromal tumor family (MESTF) of the kidney.Methods:From January 2009 to September 2021, 42 patients with pathologically-proven MESTF from the First Medical Center of Chinese PLA General Hospital were collected in this retrospective study. Clinical information, MRI features, and pathological results were documented. According to the Bosniak classification (BC) version 2019, all MESTFs were divided into cystic MESTFs (36 cases) and solid-cystic MESTFs (6 cases). The R.E.N.A.L. nephrometry score (RNS), lesion size, laterality, location, margin, shape, growth pattern, presence of protruding into renal sinus, hemorrhage, and enhancement pattern were evaluated and documented. Based on BC versions 2005 and 2019, all the cystic MESTFs were assessed and divided into low (Ⅰ, Ⅱ, ⅡF) and high (Ⅲ, Ⅳ) grades. The independent sample t test or Mann-Whitney U test were performed to compare age, RNS, and lesion size between cystic MESTFs and solid-cystic MESTFs. Pearson χ 2 test, continuity-adjusted χ 2 test or Fisher exact probability test were utilized to evaluated the differences of clinical and MRI features and the distribution of low or high grades in two versions of BC. Results:Forty-two MESTFs were unilateral and solitary masses, 25 males and 17 females, with a mean age of (41±13) years old. Compared to solid-cystic MESTFs, cystic MESTFs were prone to demonstrate endophytic growth pattern (χ 2=17.77, P<0.001), and no significant differences in other clinical and MRI features were observed between cystic and solid-cystic MESTFs (all P>0.05). There were 7 low-grade and 29 high-grade tumors in the BC version 2005, respectively. Meanwhile, 24 low-grade and 12 high-grade tumors in the BC version 2019, respectively. The distribution of low or high-grade tumors in the two versions of BC had a statistically significant difference (χ 2=16.37, P<0.001). Conclusion:MESTFs demonstrated middle-age onset and no gender predilection. Cystic MESTFs are more likely to exhibit endophytic growth pattern with low-grade classification in BC system version 2019.

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Abstract The large intestinal flora is interdependent and mutually restricted, and synergistically participates in the physiological metabolism of the body and the digestion of nutrients. The study on intestinal flora and cardiovascular health has become a very important research field. Changes in intestinal flora composition, metabolites and toxins produced by intestinal flora can cause cardiovascular system lesions. Cardiovascular disease(CVD) has become a major health problem due to high morbidity and mortality. The changes in specific intestinal flora have been identified as the key factors in the occurrence and development of CVD. However, the underlying mechanism of how intestinal flora and metabolites produce and affect CVD remains unclear. In this paper, the latest research progress of intestinal flora in regulating CVD through the intestinal cardiac axis are reviewed, focusing on the complex interaction between intestinal microorganisms and their metabolites and the occurrence and development of CVD, as well as the effect of changes in intestinal flora imbalance on the occurrence of cardiovascular events, to discuss a causal link between intestinal flora and the pathogenesis of CVD.